Synthesis of indano[60]fullerene thioketone and its application in organic solar cells.

Evaporable indano[60]fullerene ketone (FIDO) was converted to indano[60]fullerene thioketone (FIDS) in high yield by using Lawesson's reagent. Three compounds with different substituents in para position were successfully converted to the corresponding thioketones, showing that the reaction tolerates compounds with electron-donating and electron-withdrawing substituents. Computational studies with density functional theory revealed the unique vibrations of the thioketone group in FIDS. The molecular structure of FIDS was confirmed by single-crystal X-ray analysis. Bulk heterojunction organic solar cells using three evaporable fullerene derivatives (FIDO, FIDS, C60) as electron-acceptors were compared, and the open-circuit voltage with FIDS was 0.16 V higher than that with C60.

RNA m6A methylation and regulatory proteins in pulmonary arterial hypertension.

m6A (N6­methyladenosine) is the most common and abundant apparent modification in mRNA of eukaryotes. The modification of m6A is regulated dynamically and reversibly by methyltransferase (writer), demethylase (eraser), and binding protein (reader). It plays a significant role in various processes of mRNA metabolism, including regulation of transcription, maturation, translation, degradation, and stability. Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary vascular disease characterized by abnormal proliferation of pulmonary artery smooth muscle cells. Despite the existence of several effective and targeted therapies, there is currently no cure for PAH and the prognosis remains poor. Recent studies have highlighted the crucial role of m6A modification in cardiovascular diseases. Investigating the role of RNA m6A methylation in PAH could provide valuable insights for drug development. This review aims to explore the mechanism and function of m6A in the pathogenesis of PAH and discuss the potential targeting of RNA m6A methylation modification as a treatment for PAH.

Ecological and human health hazards of soil heavy metals after wildfire: A case study of Liangshan Yi autonomous prefecture, China.

Soil samples were collected in at different depths from the conflagration area in Liangshan Yi Autonomous Region, China, to investigate the distribution characteristics and ecological and human health risks of heavy metals after a wildfire. The samples collected comprise wildfire ash (WA) above the soil surface, ash soil (AS) 0-5 cm, and plain soil (PS) 5-15 cm below the soil surface. Additionally, reference soil (RS) was collected from a nearby unburned area at the same latitude as the conflagration area. The results showed that the concentrations of zinc (Zn), copper (Cu), lead (Pb), and cadmium (Cd) in the WA and AS were significantly higher than in reference soil (RS) (p < 0.05). Concentrations of Pb in the PS were 2.52 times higher than that in RS (17.9 mg kg-1) (p < 0.05). The AS and WA had the highest Index of potential ecological risks (RI > 600). In addition, The Cd in AS and WA contributed the most to the highest Improved nemerow index (INI) and RI with a contribution of more than 80%. The concentration of heavy metals was used to establish non-carcinogenic effects and cancer risks in humans via three exposure pathways: accident ingestion of soil, dermal contact with soil, and inhalation of soil particles. Hazard index (HI) values of each sample were all less than 1, indicating the non-carcinogenic risk was within the acceptable range and would not adversely affect the local population's health. The Cancer risk (CR) values of Cr, As, Cd, and Ni were all below 1 × 10-6, indicating that heavy metal pollution from this wildfire did not pose a cancer risk to residents.

Pollution and source-specific risk analysis of potentially toxic metals in urban soils of an oasis-tourist city in northwest China.

Source-specific risk apportionment for soil potentially toxic metals (PTMs) is of great significance for contamination prevention and risk management in urban environments. Eighty-five urban soil samples were obtained from an oasis-tourist city, China and examined for eight PTMs (As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn). The pollution levels, sources, and ecological risk of soil PTMs were quantified, and their source-specific ecological and human health effects were also estimated using the multi-proxy approaches. The results demonstrated that accumulation of Cd, Hg, Pb, Cr, Cu, and Zn in soils was observed compared to their background levels, and the soils experienced varying degrees of PTMs pollution, especially at sites with high-intensity anthropogenic activities. Natural sources, atmospheric deposition, industrial sources, vehicular emissions, and comprehensive inputs were the principal sources, with contributions of 29.28%, 25.86%, 20.13%, 16.50%, and 8.23%, respectively. The integrated ecological risks of PTMs in soils were moderate at most sites, with atmospheric deposition being the dominant contributor to ecological risks. Children exhibited pronounced non-cancer risks, but adults had no notable non-cancer risks. Moreover, there were potential carcinogenic risks for both children and adults within the study region. Non-cancer and carcinogenic risks were more significant for children than adults, and traffic emissions were the primary contributor to non-cancer risks (adults: 20.53%, children: 20.49%) and carcinogenic risks (adults: 22.95%, children: 22.08%). The industrial and traffic activities were considered as priority control sources for soil pollution control and risk management, with Hg, Cd, Zn, and Pb corresponding to the priority elements. This study highlights the source-specific ecological and human health effects of PTMs pollution in urban soils, thereby providing valuable information for targeted pollution control and priority source management.

Role of macrophages in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary vascular disease characterized by progressive pulmonary artery pressure elevation, increased pulmonary vascular resistance and ultimately right heart failure. Studies have demonstrated the involvement of multiple immune cells in the development of PAH in patients with PAH and in experimental PAH. Among them, macrophages, as the predominant inflammatory cells infiltrating around PAH lesions, play a crucial role in exacerbating pulmonary vascular remodeling in PAH. Macrophages are generally polarized into (classic) M1 and (alternative) M2 phenotypes, they accelerate the process of PAH by secreting various chemokines and growth factors (CX3CR1, PDGF). In this review we summarize the mechanisms of immune cell action in PAH, as well as the key factors that regulate the polarization of macrophages in different directions and their functional changes after polarization. We also summarize the effects of different microenvironments on macrophages in PAH. The insight into the interactions between macrophages and other cells, chemokines and growth factors may provide important clues for the development of new, safe and effective immune-targeted therapies for PAH.

Baicalein ameliorates Alzheimer's disease via orchestration of CX3CR1/NF-κB pathway in a triple transgenic mouse model.

Alzheimer's disease (AD) is a common chronic neurodegenerative disease. Some studies have suggested that dysregulation of microglia activation and the resulting neuroinflammation play an important role in the development of AD pathology. Activated microglia have both M1 and M2 phenotypes and inhibition of M1 phenotype while stimulating M2 phenotype has been considered as a potential treatment for neuroinflammation-related diseases. Baicalein is a class of flavonoids with anti-inflammatory, antioxidant and other biological activities, but its role in AD and the regulation of microglia are limited. The purpose of this study was to investigate the effect of baicalein on the activation of microglia in AD model mice and the related molecular mechanism. Our results showed that baicalein significantly improved the learning and memory ability and AD-related pathology of 3 × Tg-AD mice, inhibited the level of pro-inflammatory factors TNF-α, IL-1ß and IL-6, promoted the production of anti-inflammatory factors IL-4 and IL-10, and regulated the microglia phenotype through CX3CR1/NF-κB signaling pathway. In conclusion, baicalein can regulate the phenotypic transformation of activated microglia and reduce neuroinflammation through CX3CR1/NF-κB pathway, thereby improving the learning and memory ability of 3 × Tg-AD mice.

Network meta-analysis of SGLT-2 inhibitor-induced hypoglycemia risk in type 2 diabetes patients / 中国药房

OBJECTIVE To evaluate the risk of hypoglycemia caused by sodium-glucose co-transporter protein 2 （SGLT-2） inhibitors in type 2 diabetes （T2DM） patients. METHODS Retrieved from PubMed， Web of Science， Cochrane Library， CNKI， VIP， Wanfang Data and CBM， randomized controlled trials （RCTs） about SGLT-2 inhibitors in the treatment of T2DM were collected from the inception to Oct. 15th， 2022. After literature screening， data extraction and quality evaluation of included literature with bias risk assessment tool recommended by the Cochrane system evaluator handbook 5.1.0， Stata 15.1 software was used for network meta-analysis and publication bias analysis. RESULTS A total of 22 RCTs were included， with a total of 18 734 patients. The results of meta-analysis showed that compared with ertugliflozin 15 mg [RR＝3.26， 95%CI （1.13， 8.11）， P＜0.05] and ertugliflozin 25 mg [RR＝3.08， 95%CI （1.12， 6.34）， P＜0.05]， the incidence of hypoglycemia was significantly increased in patients using canagliflozin 300 mg. Compared with ertugliflozin 15 mg [RR＝1.48， 95%CI （1.24， 6.93）， P＜0.05] and ertugliflozin 25 mg [RR＝6.74， 95%CI （1.33， 9.34）， P＜0.05]， the incidence of hypoglycemia in patients treated with canagliflozin 100 mg was significantly increased. There was no statistically significant difference between other groups （P＞0.05）. The ranking results of the network meta-analysis showed that the incidence of hypoglycemia was from low to high， ie. ertugliflozin 15 mg＞placebo＞ertugliflozin 25 mg＞empgaliflozin 25 mg＞empgaliflozin 10 mg＞empgaliflozin 1 mg＞dapagliflozin 5 mg＞ dapagliflozin 10 mg＞dapagliflozin 2.5 mg＞canagliflozin 300 mg＞ertugliflozin 10 mg＞ertugliflozin 5 mg＞empgaliflozin 50 mg＞canagliflozin 200 mg＞canagliflozin 100 mg＞canag-liflozin 50 mg＞ertugliflozin 1 mg＞empgaliflozin 5 mg. Results of publication bias analysis showed that there was little possibility of publication bias in this study. CONCLUSIONS When SGLT-2 inhibitors are used in patients with T2DM， the incidence of hypoglycemia is the lowest when using ertugliflozin 15 mg， and the incidence of hypoglycemia is the highest when using empagliflozin 5 mg.

An inclusion complex of cucurbit[7]uril with benzimidazolyl benzyl viologen exhibits fluorescence and photochromic properties.

In order to investigate the photochromic mechanism of photochromic materials based on supramolecular host-guest systems, we designed and synthesized a unique viologen derivative (benzimidazolyl benzyl viologen, guest 1·Cl3), which does not contain oxygen atoms. The binding interaction of guest 13+ with host cucurbit[7]uril (Q[7]) was investigated by various techniques. The obtained supramolecular host-guest complex 13+@Q[7] exhibits interesting fluorescence emission and reversible photochromism. The ESR and XPS experimental data suggest that the photochromic process of the complex 13+@Q[7] comes from the electron transfer from the carbonyl O atoms of the host Q[7] to the bipyridinium N atoms of the guest 13+.

Cornuside Is a Potential Agent against Alzheimer's Disease via Orchestration of Reactive Astrocytes.

Cornuside is an iridoid glycoside from Cornus officinalis, with the activities of anti-inflammatory, antioxidant, anti-mitochondrial dysfunction, and neuroprotection. In the present research, a triple-transgenic mice model of AD (3 × Tg-AD) was used to explore the beneficial actions and potential mechanism of cornuside on the memory deficits. We found that cornuside prominently alleviated neuronal injuries, reduced amyloid plaque pathology, inhibited Tau phosphorylation, and repaired synaptic damage. Additionally, cornuside lowered the release of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and nitric oxide (NO), lowered the level of malondialdehyde (MDA), and increased the activity of superoxide dismutase (SOD) and the level of glutathione peroxidase (GSH-Px). Cornuside also significantly reduced the activation of astrocytes and modulated A1/A2 phenotypes by the AKT/Nrf2/NF-κB signaling pathway. We further confirmed that LY294002 and Nrf2 silencing could block the cornuside-mediated phenotypic switch of C6 cells induced by microglia conditioned medium (MCM) in response to lipopolysaccharide (LPS), which indicated that the effects of cornuside in astrocyte activation are dependent on AKT/Nrf2/NF-κB signaling. In conclusion, cornuside may regulate the phenotypic conversion of astrocytes, inhibit neuroinflammation and oxidative stress, improve synaptic plasticity, and alleviate cognitive impairment in mice through the AKT/Nrf2/NF-κB axis. Our present work provides an experimental foundation for further research and development of cornuside as a candidate drug for AD management.

L-Carnitine Alleviates the Myocardial Infarction and Left Ventricular Remodeling through Bax/Bcl-2 Signal Pathway.

Purpose: L-carnitine (LC) is considered to have good therapeutic potential for myocardial infarction (MI), but its mechanism has not been clarified. The aim of the study is to elucidate the cardioprotective effects of LC in mice following MI and related mechanisms. Methods: ICR mice were treated with LC for 2 weeks after induction of MI with ligation of left anterior descending artery. Electrocardiographic (ECG) recording and echocardiography were used to evaluate cardiac function. H&E staining, TTC staining, and Masson staining were performed for morphological analysis and cardiac fibrosis. ELISA and immunofluorescence were utilized to detect biomarkers and inflammatory mediators. The key proteins in the Bax/Bcl-2 signaling pathway were also examined by Western blot. Results: Both echocardiography and histological measurement showed an improvement in cardiac function and morphology. Biomarkers such as LDH, NT-proBNP, cTnT, and AST, as well as the inflammatory cytokines IL-1ß, IL-6, and TNF-α, were decreased in plasma of mice receiving LC treatment after myocardial injury. In addition, the expression of α-SMA as well as the key proteins in the Bax/Bcl-2 signaling pathway in cardiac myocardium were much lower in mice with LC treatment compared to those without after MI. Conclusions: Our data suggest that LC can effectively ameliorate left ventricular (LV) remodeling after MI, and its beneficial effects on myocardial function and remodeling may be attributable at least in part to anti-inflammatory and inhibition of the Bax/Bcl-2 apoptotic signaling pathway.

Regulatory T Cell-Related Gene Indicators in Pulmonary Hypertension.

Objective: Regulatory T cells (Tregs) are critical immune modulators to maintain immune homeostasis and limit pulmonary hypertension (PH). This study was aimed to identify Treg-related genes (TRGs) in PH. Methods: The gene expression profile from lungs of PH patients was retrieved from the Gene Expression Omnibus (GEO) database. The abundance of Tregs was estimated by the xCell algorithm, the correlation of which with differentially expressed genes (DEGs) was performed. DEGs with a |Pearson correlation coefficient| >0.4 were identified as TRGs. Functional annotation and the protein-protein interaction (PPI) network were analyzed. A gene signature for 25 hub TRGs (TRGscore) was generated by a single sample scoring method to determine its accuracy to distinguish PH from control subjects. TRGs were validated in datasets of transcriptional profiling of PH cohorts and in lung tissues of experimental PH mice. Results: A total of 819 DEGs were identified in lungs of 58 PAH patients compared to that of 25 control subjects of dataset GSE117261. In total, 165 of all these DEGs were correlated with the abundance of Tregs and identified as TRGs, with 90 upregulated genes and 75 downregulated genes compared to that of control subjects. The upregulated TRGs were enriched in negative regulation of multiple pathways, such as cAMP-mediated signaling and I-kappaB kinase/NF-kappaB signaling, and regulated by multiple genes encoding transcriptional factors including HIF1A. Furthermore, 25 hub genes categorized into three clusters out of 165 TRGs were derived, and we identified 27 potential drugs targeting 10 hub TRGs. The TRGscore based on 25 hub TRGs was higher in PH patients and could distinguish PH from control subjects (all AUC >0.7). Among them, 10 genes including NCF2, MNDA/Ifi211, HCK, FGR, CSF3R, AQP9, S100A8, G6PD/G6pdx, PGD, and TXNRD1 were significantly reduced in lungs of severe PH patients of dataset GSE24988 as well as in lungs of hypoxic PH mice compared to corresponding controls. Conclusion: Our finding will shed some light on the Treg-associated therapeutic targets in the progression of PH and emphasize on TRGscore as a novel indicator for PH.

Luteolin alleviates cognitive impairment in Alzheimer's disease mouse model via inhibiting endoplasmic reticulum stress-dependent neuroinflammation.

Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer's disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg-1 · d-1, ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1ß, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.

Screening of lipid parameters in coronary artery disease based on LASSO regression / 中国综合临床

Objective:Using lasso regression analysis to screen out the blood lipid indexes closely related to coronary heart diseaseMethods:The clinical data of 3 062 patients with coronary heart disease who were hospitalized in the Department of Cardiology, Affiliated Hospital of Jining Medical College from May 2013 to November 2015 were retrospectively analyzed.They were divided into control group ( n=2 427) and coronary angiography group ( n=635). R language was used for statistical analysis.Multiple logistic regression models were established for indicators of blood lipid related to CAD, and their multicollinearity severity was assessed.LASSO regression was used to screen out the representative lipid parameters in the CAD prediction model. Results:A total of 3 062 patients were enrolled, including 2 427 patients in coronary heart disease group and 635 patients in control group.The inclusion of lipid parameters into multiple logistic regression model leads to serious multicollinearity.Stepwise regression can only partially reduce multicollinearity severity, while LASSO regression model significantly reduces multicollinearity severity.Low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and non-high density lipoprotein cholesterol (non-HDL-C) were found to be the representative lipid indexes for predicting coronary heart disease by LASSO regression analysis.Conclusion:LASSO regression has advantages in processing multicollinearity data.LASSO regression showed that LDL-C, HDL-C and non-HDL-C were representative lipid indicators for predicting coronary heart disease..

Brain function differences in drug-naïve first-episode auditory verbal hallucination-schizophrenia patients with versus without insight / 中华医学杂志(英文版)

Background@#Few studies have reported brain function differences in drug-naïve first-episode schizophrenia patients who had auditory verbal hallucinations (AVH) with insight vs. those without insight. This study aimed to investigate brain function differences between drug-naïve first-episode AVH-schizophrenia patients with and without insight.@*Methods@#Forty first-episode drug-naïve AVH-schizophrenia patients with or without insight and 40 healthy controls between December 2016 and December 2018 were recruited in this study. The auditory hallucinations rating scale (AHRS) was used to assess AVH severity, while the insight and treatment attitudes questionnaire was used to distinguish insight. The global functional connectivity density (gFCD) between different groups was compared using a voxel-wise one-way analysis of covariance. The relationship between gFCD and AHRS total scores were analyzed using voxel-wise multiple regression.@*Results@#Finally, 13 first-episode drug-naïve AVH-schizophrenia patients with insight, 15 AVH-schizophrenia patients without insight, and 20 healthy controls were included for analysis. Except for global assessment of functioning scores, there were no significant differences in sociodemographic information between the AVH-schizophrenia and healthy groups (P > 0.05). Compared to the healthy controls, AVH-schizophrenia patients with insight demonstrated a decreased gFCD in the supramarginal gyrus within the primary auditory cortex, while those without insight demonstrated an increased gFCD in the inferior frontal gyrus and superior temporal gyrus and decreased gFCD in the supplemental motor area. Compared to the AVH-schizophrenia patients with insight, those without insight demonstrated an increased gFCD in the supra-marginal gyrus and posterior superior temporal lobule and a decreased gFCD in the frontal lobe. No significant correlation between gFCD and AVH severity (AHRS total score: r = 0.23, P = 0.590; and frequency: r = 0.42, P = 0.820) was found in both AVH-schizophrenia groups.@*Conclusions@#The gFCD-aberrant brain regions in the AVH-schizophrenia patients without insight were wider compared to those with insight, although the AHRS scores were not significantly different. The AVH-schizophrenia patients without insight had wide functional impairment in the frontal lobule, which may underlie the lack of insight and the abnormal hyperactivity in the inferior frontal gurus and temporal lobe related to the AVH symptoms.

Brain function differences in drug-naïve first-episode auditory verbal hallucination-schizophrenia patients with versus without insight / 中华医学杂志(英文版)

BACKGROUND@#Few studies have reported brain function differences in drug-naïve first-episode schizophrenia patients who had auditory verbal hallucinations (AVH) with insight vs. those without insight. This study aimed to investigate brain function differences between drug-naïve first-episode AVH-schizophrenia patients with and without insight.@*METHODS@#Forty first-episode drug-naïve AVH-schizophrenia patients with or without insight and 40 healthy controls between December 2016 and December 2018 were recruited in this study. The auditory hallucinations rating scale (AHRS) was used to assess AVH severity, while the insight and treatment attitudes questionnaire was used to distinguish insight. The global functional connectivity density (gFCD) between different groups was compared using a voxel-wise one-way analysis of covariance. The relationship between gFCD and AHRS total scores were analyzed using voxel-wise multiple regression.@*RESULTS@#Finally, 13 first-episode drug-naïve AVH-schizophrenia patients with insight, 15 AVH-schizophrenia patients without insight, and 20 healthy controls were included for analysis. Except for global assessment of functioning scores, there were no significant differences in sociodemographic information between the AVH-schizophrenia and healthy groups (P > 0.05). Compared to the healthy controls, AVH-schizophrenia patients with insight demonstrated a decreased gFCD in the supra-marginal gyrus within the primary auditory cortex, while those without insight demonstrated an increased gFCD in the inferior frontal gyrus and superior temporal gyrus and decreased gFCD in the supplemental motor area. Compared to the AVH-schizophrenia patients with insight, those without insight demonstrated an increased gFCD in the supra-marginal gyrus and posterior superior temporal lobule and a decreased gFCD in the frontal lobe. No significant correlation between gFCD and AVH severity (AHRS total score: r = 0.23, P = 0.590; and frequency: r = 0.42, P = 0.820) was found in both AVH-schizophrenia groups.@*CONCLUSIONS@#The gFCD-aberrant brain regions in the AVH-schizophrenia patients without insight were wider compared to those with insight, although the AHRS scores were not significantly different. The AVH-schizophrenia patients without insight had wide functional impairment in the frontal lobule, which may underlie the lack of insight and the abnormal hyperactivity in the inferior frontal gurus and temporal lobe related to the AVH symptoms.

Wenyang Huoxue Jiedu formula inhibits thin-cap fibroatheroma plaque formation via the VEGF/VEGFR signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: For many years, Guangzhou University of Chinese Medicine has been successfully using the empirical Wenyang Huoxue Jiedu formula (WHJF) to treat coronary heart disease. Modern theories of acute coronary syndrome mainly focus on rupture of thin-cap fibroatheromas (TCFAs), which is closely related to the release of vascular endothelial growth factor and its receptor (VEGF/VEGFR). AIM OF STUDY: We investigated the effects of WHJF on the formation of TCFA plaques and the potential mechanism (VEGF/VEGFR signaling pathway). MATERIALS AND METHODS: For the in vivo experiments, WHJF was administered to ApoE-/- mice, as a model of TCFA plaque formation. Aortic sections of the mice were obtained, and the vulnerability index and new vessel density of plaques were calculated by the Movat staining assay and immunohistochemistry kit, respectively. Protein and mRNA expression levels of VEGF/VEGFR in aortas were assayed by capillary electrophoresis immunoassay and quantitative real-time polymerase chain reaction analyses. In vitro, WHJF serum was produced in rats on the fourth day 2 h after the first administration of different concentrations of WHJF. Proliferation, migration, and lumen formation ability of human umbilical vein endothelial cells (HUVECs) treated with sera from these rats were assayed by the CKK-8 kit, Transwell plates, and Matrigel assay, respectively. Protein and mRNA expression levels of signaling molecules in the VEGF/VEGFR pathways were also examined. RESULTS: In vivo, the vulnerability index and new vessel density of plaques in the WHJF group were lower than those values in the blank control group (P < 0.05). No differences were found between the groups in the expression levels of VEGF/VEGFR (P > 0.05). In vitro, the proliferation, migration, and tube formation of HUVECs in the high-dose WHJF group were reduced compared to the control group (P < 0.05). This finding was in agreement with the downregulation of VEGFR-2 and pERK (P < 0.05). The mRNA expression of signaling molecules showed no difference between the groups (P > 0.05). CONCLUSIONS: WHJF inhibits TCFA formation by influencing the VEGF/VEGFR signaling pathway.

The progresses and perspectives of the control and eradication of persistent bacteria / 医学研究生学报

Persistent bacteria is a microbial subpopulation which can survive from lethal concentration of antimicrobial agents. Unlike the resistant bacteria which usually acquire the resistance from heritable gene mutations, persisters are genetically identical to regular cells in genome but show a distinct antibiotic tolerant phenotype through a state of dormancy. Once the antimicrobial therapy is removed,the persisters can regrow to a new population and cause the recurrent infectious diseases. The increased threats due to the in-fections and drug tolerance caused by persistent bacteria promote the interests of preventing bacterial persistence. This review discusses the harmfulness of persistent infections, the mechanisms of bacterial persistence and summarizes the different control and eradication strategies,aiming to provide ideas and references for further research.

Quaternary ammonium-induced multidrug tolerant Streptococcus mutans persisters elevate cariogenic virulence in vitro.

Dental caries are the most prevalent chronic infections in the oral cavity, and Streptococcus mutans acts as the main cariogenic bacterial species. Antibacterial quaternary ammonium compounds (QAs) have been developed to preveFnt or treat dental caries. However, there is no report on the tolerance of S. mutans to QAs. In this study, we investigated the development of S. mutans persistence induced by a novel dental caries defensive agent, dimethylaminododecyl methacrylate (DMADDM), for the first time. Typical biphasic killing kinetics for persisters were observed in both S. mutans planktonic and biofilm cultures challenged by DMADDM at concentrations of 20 and 200 µg·mL-1, respectively. The persisters tolerated six other antibiotics with different antibacterial mechanisms, while only daptomycin and vancomycin could slightly reduce the persister numbers in planktonic cultures. The distribution of persisters in DMADDM-treated biofilms was similar to that in the untreated control, except that the total biomass and biofilm height were significantly reduced. A higher exopolysaccharides (EPS):bacteria ratio was observed in DMADDM-treated biofilms. Persisters in biofilms significantly upregulated gtf gene expression, indicating an increase in the bacteria's ability to produce EPS and an elevated capability of cariogenic virulence. Carbon source metabolism was significantly reduced, as related metabolic genes were all downregulated in persisters. Concentrations of 0.1 mM, 1 mM and 10 mM of extra glucose significantly reduced the number of persisters both in planktonic and biofilm conditions. The formation of non-inheritable and multidrug tolerant persisters induced by DMADDM suggested that drug tolerance and new persistent eradication strategies should be considered for oral antibacterial agents.

Correlation between Chromosomal Abnormality and Cell Morphology with Myelodysplastic Syndrome Patients / 现代检验医学杂志

Objective To investigate the correlation between morphological abnormalities and abnormal myelodysplastic syn-dromes(MDS)cloning.Methods 82 cases of MDS were collected with complete FISH and morphological abnormalities. The relationship between MDS cell morphology and chromosome abnormality was investigated.Results 45 cases of chromo-somal abnormalities were found,and +8 were the most frequent chromosomal abnormalities.8 cases were +8,-5 and 5q-were 6,20q-were 7,-7 and 7q-were 5,complex karyotypes(>3 abnormalities)were 6.There were statistically significant differences in the proportion of primordial cells,megakaryocyte dysplasia,megakaryocyte abnormalities between karyotype abnormal group and karyotype normal group(P<0.05).There were statistically significant differences in the proportion of abnormal karyotype among high risk group and low risk group,the low risk group and medium risk group(P<0.05).Con-clusion The chromosomal abnormalities of MDS patients would be related to morphological changes.

Antidepressant Effects of Electroconvulsive Therapy Unrelated to the Brain's Functional Network Connectivity alterations at an Individual Level / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Electroconvulsive therapy (ECT) can alleviate the symptoms of treatment-resistant depression (TRD). Functional network connectivity (FNC) is a newly developed method to investigate the brain's functional connectivity patterns. The first aim of this study was to investigate FNC alterations between TRD patients and healthy controls. The second aim was to explore the relationship between the ECT treatment response and pre-ECT treatment FNC alterations in individual TRD patients.</p><p><b>METHODS</b>This study included 82 TRD patients and 41 controls. Patients were screened at baseline and after 2 weeks of treatment with a combination of ECT and antidepressants. Group information guided-independent component analysis (GIG-ICA) was used to compute subject-specific functional networks (FNs). Grassmann manifold and step-wise forward component selection using support vector machines were adopted to perform the FNC measure and extract the functional networks' connectivity patterns (FCP). Pearson's correlation analysis was used to calculate the correlations between the FCP and ECT response.</p><p><b>RESULTS</b>A total of 82 TRD patients in the ECT group were successfully treated. On an average, 8.50 ± 2.00 ECT sessions were conducted. After ECT treatment, only 42 TRD patients had an improved response to ECT (the Hamilton scores reduction rate was more than 50%), response rate 51%. 8 FNs (anterior and posterior default mode network, bilateral frontoparietal network, audio network, visual network, dorsal attention network, and sensorimotor network) were obtained using GIG-ICA. We did not found that FCPs were significantly different between TRD patients and healthy controls. Moreover, the baseline FCP was unrelated to the ECT treatment response.</p><p><b>CONCLUSIONS</b>The FNC was not significantly different between the TRD patients and healthy controls, and the baseline FCP was unrelated to the ECT treatment response. These findings will necessitate that we modify the experimental scheme to explore the mechanisms underlying ECT's effects on depression and explore the specific predictors of the effects of ECT based on the pre-ECT treatment magnetic resonance imaging.</p>